U.S. patent application number 12/620132 was filed with the patent office on 2010-03-11 for physical conditioning system, device and method.
Invention is credited to Andrew P. Kramer, Imad Libbus, Joseph M. Pastore, Julio C. Spinelli.
Application Number | 20100063564 12/620132 |
Document ID | / |
Family ID | 38822888 |
Filed Date | 2010-03-11 |
United States Patent
Application |
20100063564 |
Kind Code |
A1 |
Libbus; Imad ; et
al. |
March 11, 2010 |
PHYSICAL CONDITIONING SYSTEM, DEVICE AND METHOD
Abstract
Various system embodiments comprise a neural stimulator and a
controller. The neural stimulator is adapted to generate a
stimulation signal adapted to elicit sympathetic activity at a
neural target. The controller is adapted to control the neural
stimulator to provide a physical conditioning therapy. The
controller is adapted to control the neural stimulator to
intermittently elicit sympathetic activity at the neural target.
Other aspects and embodiments are provided herein.
Inventors: |
Libbus; Imad; (St. Paul,
MN) ; Spinelli; Julio C.; (Buenos Aires, AR) ;
Pastore; Joseph M.; (Concord, OH) ; Kramer; Andrew
P.; (Marine on St. Croix, MN) |
Correspondence
Address: |
SCHWEGMAN, LUNDBERG & WOESSNER/BSC-CRM
PO BOX 2938
MINNEAPOLIS
MN
55402
US
|
Family ID: |
38822888 |
Appl. No.: |
12/620132 |
Filed: |
November 17, 2009 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
11423249 |
Jun 9, 2006 |
7647101 |
|
|
12620132 |
|
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Current U.S.
Class: |
607/62 |
Current CPC
Class: |
A61N 1/36014 20130101;
A61N 1/37288 20130101; A61N 1/37282 20130101; A61N 1/36114
20130101; A61N 2001/0585 20130101 |
Class at
Publication: |
607/62 |
International
Class: |
A61N 1/00 20060101
A61N001/00 |
Claims
1. A system, comprising: means for providing a physical
conditioning therapy, wherein the means for providing the physical
condition therapy includes: a memory programmed with instructions
for delivering a physical conditioning therapy that elicits
sympathetic activity correlated to an exercise regimen to mimic a
sympathetic response to the exercise program; and means performing
the instructions to elicit sympathetic activity correlated to the
exercise regimen to mimic the sympathetic response to the exercise
regimen, wherein the means for eliciting the sympathetic activity
includes means for intermittently stimulating a neural target to
elicit the sympathetic activity correlated to the exercise
regimen.
2. The system of claim 1, further comprising means for integrating
the physical conditioning therapy with an anti-hypertension therapy
(AHT).
3. The system of claim 1, further comprising means for integrating
the physical conditioning therapy with an anti-remodeling therapy
(ART).
4. The system of claim 1, further comprising means for adjusting
neural stimulation parameters to achieve a target physiological
response to the physical conditioning therapy.
5. The system of claim 1, further comprising means for terminating
the physical conditioning therapy in response to an adverse
physiological response.
6. The system of claim 1, wherein the means for intermittently
stimulating a neural target to elicit the sympathetic activity
includes means for eliciting the sympathetic activity for a time
period on the order of two hours or less for each episode of the
physical conditioning therapy.
7. The system of claim 1, wherein the instructions programmed in
the memory include instructions to intermittently elicit
sympathetic activity according to a predetermined schedule.
8. The system of claim 1, further comprising means for sensing a
physiological response indicative of the elicited sympathetic
activity.
9. The system of claim 1, wherein the means for intermittently
stimulating a neural target to elicit the sympathetic activity
correlated to the exercise regimen includes means for
intermittently eliciting sympathetic activity by stimulating neural
traffic at a sympathetic neural target.
10. The system of claim 9, wherein the sympathetic neural target
includes a peroneal nerve, a sympathetic column in a spinal cord,
or cardiac post-ganglionic sympathetic neurons.
11. The system of claim 1, wherein the instructions programmed in
the memory include instructions to, when operated on by the
controller, control the neural stimulator to intermittently elicit
sympathetic activity by inhibiting neural traffic at a
parasympathetic neural target.
12. The system of claim 11, wherein the parasympathetic neural
target includes a vagus nerve, a baroreceptor, or a cardiac fat
pad.
13. The system of claim 1, further comprising means for providing a
second neural stimulation therapy adapted to elicit a
parasympathetic response; and means for simultaneously delivering
the physical conditioning therapy and the second neural stimulation
therapy.
14. The system of claim 1, further comprising means for responding
to a signal triggered by a user to initiate a session of the
physical conditioning therapy.
15. The system of claim 1, further comprising means for responding
to a signal triggered by a user to terminate a session of the
physical conditioning therapy.
16. The system of claim 1, further comprising means or responding
to a signal triggered by a user to titrate the physical
conditioning therapy.
17. The system of claim 1, further comprising means for adjusting
neural stimulation parameters to achieve a target physiological
response to the physical conditioning therapy.
18. The system of claim 17, wherein the target physiological
response includes a target heart rate.
19. The system of claim 17, wherein the target physiological
response includes a target blood pressure.
20. The system of claim 17, wherein the target physiological
response includes a target respiration.
Description
CROSS REFERENCE TO RELATED APPLICATION
[0001] This application is a continuation of U.S. application Ser.
No. 11/423,249, filed Jun. 9, 2006, which is hereby incorporated by
reference in its entirety.
FIELD OF THE INVENTION
[0002] This application relates generally to medical devices and,
more particularly, to systems, devices and methods for providing
physical conditioning.
BACKGROUND
[0003] Dobutamine is a synthetic derivative of dopamine
characterized by prominent inotropic but weak chronotropic and
arrhythmogenic properties. Dopamine is a precursor of
norepinephrine and epinephrine; and dopamine, norepinephrine and
epinephrine are catecholamines associated with a sympathetic
response to stress. Dobutamine provides a pharmaceutical means for
providing sympathomimetic stimulation (stimulation that mimics the
actions of the sympathetic system).
[0004] Animal studies have shown that intermittent sympathomimetic
stimulation with dobutamine can produce beneficial changes
analogous to the effects of physical training. In a controlled
study of moderate to severe heart failure patients, short-term
sympathetic stimulation with dobutamine (30 minutes/day, 4
days/week, for 3 weeks), was associated with a significant
improvement in symptoms, autonomic balance, and chronotropic
detrimental down-regulation responsiveness. Benefits of short-term
sympathetic stimulation with dobutamine included increased exercise
tolerance, improved heart rate variability, lowered peripheral
vascular resistance, and reduced plasma noradrenaline. The short
stimulation periods, in contrast to studies with long-term dopamine
infusion, were not associated with detrimental down-regulation of
B-receptors.
SUMMARY
[0005] Various aspects of the present subject matter relate to a
system. Various system embodiments comprise a neural stimulator and
a controller. The neural stimulator is adapted to generate a
stimulation signal adapted to elicit sympathetic activity at a
neural target. The controller is adapted to control the neural
stimulator to provide a physical conditioning therapy. The
controller is adapted to control the neural stimulator to
intermittently elicit sympathetic activity at the neural
target.
[0006] Various aspects of the present subject matter relate to a
method. According to various embodiments of the method, a physical
conditioning therapy is provided. Providing a physical conditioning
therapy includes intermittently stimulating a neural target to
elicit a sympathetic response.
[0007] This Summary is an overview of some of the teachings of the
present application and not intended to be an exclusive or
exhaustive treatment of the present subject matter. Further details
about the present subject matter are found in the detailed
description and appended claims. Other aspects will be apparent to
persons skilled in the art upon reading and understanding the
following detailed description and viewing the drawings that form a
part thereof, each of which are not to be taken in a limiting
sense. The scope of the present invention is defined by the
appended claims and their equivalents.
BRIEF DESCRIPTION OF THE DRAWINGS
[0008] FIG. 1 illustrates a method for providing physical
conditioning, according to various embodiments of the present
subject matter.
[0009] FIG. 2 illustrates a method for providing physical
conditioning, according to various embodiments of the present
subject matter.
[0010] FIG. 3 illustrates a physical conditioning therapy using
sympathetic stimulation and/or parasympathetic inhibition,
according to various embodiments of the present subject matter.
[0011] FIGS. 4-5 illustrate examples of therapy protocols that
combine or integrate sympathetic stimulation and/or parasympathetic
inhibition associated with physical conditioning with therapies
that use parasympathetic stimulation and/or sympathetic inhibition,
according to various embodiments of the present subject matter.
[0012] FIGS. 6A-6B illustrate a heart and lead arrangements to
provide both myocardial and neural stimulation, according to
various embodiments of the present subject matter.
[0013] FIGS. 7A-7B illustrate a heart, including cardiac fat pads
which are stimulated in various embodiments of the present subject
matter.
[0014] FIG. 8 illustrates an implantable medical device (IMD),
according to various embodiments of the present subject matter.
[0015] FIG. 9 illustrates an implantable medical device (IMD)
having a neural stimulation (NS) component and cardiac rhythm
management (CRM) component, according to various embodiments of the
present subject matter.
[0016] FIG. 10 shows a system diagram of an embodiment of a
microprocessor-based implantable device, according to various
embodiments.
[0017] FIG. 11 illustrates a system including an implantable
medical device (IMD) and an external system or device, according to
various embodiments of the present subject matter.
[0018] FIG. 12 illustrates a system including an external device,
an implantable neural stimulator (NS) device and an implantable
cardiac rhythm management (CRM) device, according to various
embodiments of the present subject matter.
[0019] FIG. 13 illustrates an IMD placed subcutaneously or
submuscularly in a patient's chest with a lead positioned to
provide cardiac post-ganglionic sympathetic nerve plexus
stimulation, and with a lead positioned to stimulate and/or inhibit
neural traffic in a vagus nerve, by way of example and not by way
of limitation, according to various embodiments.
[0020] FIG. 14 illustrates an IMD with a lead positioned to provide
cardiac post-ganglionic sympathetic nerve plexus stimulation, and
with satellite transducers positioned to stimulate/inhibit neural
targets, according to various embodiments.
[0021] FIG. 15 illustrates a leg, and further illustrates a nerve
stimulator adapted to stimulate a peroneal nerve in the leg.
[0022] FIG. 16 is a block diagram illustrating an embodiment of an
external system.
DETAILED DESCRIPTION
[0023] The following detailed description of the present subject
matter refers to the accompanying drawings which show, by way of
illustration, specific aspects and embodiments in which the present
subject matter may be practiced. These embodiments are described in
sufficient detail to enable those skilled in the art to practice
the present subject matter. Other embodiments may be utilized and
structural, logical, and electrical changes may be made without
departing from the scope of the present subject matter. References
to "an", "one", or "various" embodiments in this disclosure are not
necessarily to the same embodiment, and such references contemplate
more than one embodiment. The following detailed description is,
therefore, not to be taken in a limiting sense, and the scope is
defined only by the appended claims, along with the full scope of
legal equivalents to which such claims are entitled.
[0024] Some medical device embodiments stimulate a sympathetic
neural target to provide the physical conditioning therapy, some
medical device embodiments inhibit a parasympathetic neural target
to provide physical conditioning therapy, and some medical device
embodiments provide both sympathetic stimulation and
parasympathetic inhibition for a physical conditioning therapy.
Various embodiments provide an external neural stimulator to
transcutaneously provide the neural stimulation and/or inhibition,
and various embodiments provide an internal neural stimulator to
provide the neural stimulation and/or inhibition. Examples of
neural targets to provide sympathetic stimulation include the
sympathetic column in the spinal cord, cardiac post-ganglionic
sympathetic neurons, and the peroneal nerve behind the knee.
Examples of a neural target to provide parasympathetic inhibition
include vagus, aortic and carotid nerves and branches thereof,
cardiac fat pads, and baroreceptors such as baroreceptors in the
aortic arch or carotid sinus. These neural target examples are not
intended to be an exhaustive list of all possible neural targets.
According to various embodiments, efferent and/or afferent neural
pathways can serve as targets.
[0025] Various embodiments provide an electrical vector between two
electrodes or among multiple electrodes to provide the stimulation
or inhibition of nerve traffic. Other means for stimulating or
inhibiting nerve traffic can be used. For example, ultrasound
stimulation, light stimulation and magnetic stimulation of nerves
have been proposed.
[0026] Various embodiments provide a programmable pulse generator
to deliver intermittent short periods of sympathetic stimulation
and/or parasympathetic inhibition to mimic the effects of physical
training. For example, the physical conditioning provided by the
sympathetic stimulation and/or parasympathetic inhibition can occur
on a daily basis for about 30 minutes/day. The therapy is of a
relatively short duration. Embodiments provide therapy on the order
of 2 hours or less. The physical conditioning therapy provided by
the neural stimulation device can be programmed to correlate to a
suitable exercise regimen for the patient. For example, the
above-identified 30 minutes/day of neural stimulation can
correspond to 30 minutes/day of walking In another embodiment, by
way of example, the present subject matter can provide physical
conditioning therapy that corresponds to an every other day
exercise regimen. In an embodiment, a patient or health-care
provider controls the times when the therapy is initiated and
terminated. Safety measures can be provided to prevent therapies of
excessive duration. Closed-loop feedback of a physiological
variable can be used to acutely titrate the therapy to achieve a
desired response (e.g. to achieve and maintain a target heart rate
zone during exercise or achieve a desired heart rate profile in
which the heart rate increases and decreases) or abruptly terminate
the therapy when the physiological response is adverse or otherwise
indicates that the patient is not tolerating the therapy. The
feedback can be used to adjust the intensity of the sympathetic
stimulation/parasympathetic inhibition by appropriately adjusting
the frequency and duration of the periods of sympathetic
stimulation, and/or adjusting stimulation parameters.
[0027] Embodiments of the present subject matter provide heart
failure therapy using physical conditioning. However, physical
conditioning via sympathetic stimulation/parasympathetic inhibition
is applied to any patient who may benefit from physical
conditioning, but is unable to tolerate physical exercise. The
present subject matter can be incorporated as a stand-alone neural
stimulator, or integrated into an existing CRM device for
comprehensive heart failure therapy, for example.
[0028] The remainder of this disclosure further elaborates on
aspects and embodiments of the present subject matter. An overview
of some physiology is provided to assist with understanding
physical conditioning therapy and other therapies discussed
thereafter. Some embodiments combine or integrate physical
conditioning therapy with other therapies. Also discussed below are
device embodiments and system embodiments.
Physiology
[0029] In addition to being used to provide physical conditioning
therapy, the nervous system can be used to provide therapy for
heart failure, hypertension, and cardiac remodeling. Therefore,
this brief overview includes a brief discussion of the nervous
system, heart failure, hypertension and cardiac remodeling.
Nervous System
[0030] The automatic nervous system (ANS) regulates "involuntary"
organs, while the contraction of voluntary (skeletal) muscles is
controlled by somatic motor nerves. Examples of involuntary organs
include respiratory and digestive organs, and also include blood
vessels and the heart. Often, the ANS functions in an involuntary,
reflexive manner to regulate glands, to regulate muscles in the
skin, eye, stomach, intestines and bladder, and to regulate cardiac
muscle and the muscle around blood vessels, for example.
[0031] The ANS includes, but is not limited to, the sympathetic
nervous system and the parasympathetic nervous system. The
sympathetic nervous system is affiliated with stress and the "fight
or flight response" to emergencies. Among other effects, the "fight
or flight response" increases blood pressure and heart rate to
increase skeletal muscle blood flow, and decreases digestion to
provide the energy for "fighting or fleeing." The parasympathetic
nervous system is affiliated with relaxation and the "rest and
digest response" which, among other effects, decreases blood
pressure and heart rate, and increases digestion to conserve
energy. The ANS maintains normal internal function and works with
the somatic nervous system. Afferent nerves convey impulses toward
a nerve center, and efferent nerves convey impulses away from a
nerve center.
[0032] The heart rate and force is increased when the sympathetic
nervous system is stimulated, and is decreased when the sympathetic
nervous system is inhibited (the parasympathetic nervous system is
stimulated). Cardiac rate, contractility, and excitability are
known to be modulated by centrally mediated reflex pathways.
Baroreceptors and chemoreceptors in the heart, great vessels, and
lungs, transmit cardiac activity through vagal and sympathetic
afferent fibers to the central nervous system. Activation of
sympathetic afferents triggers reflex sympathetic activation,
parasympathetic inhibition, vasoconstriction, and tachycardia. In
contrast, parasympathetic activation results in bradycardia,
vasodilation, and inhibition of vasopressin release. Among many
other factors, decreased parasympathetic or vagal tone or increased
sympathetic tone is associated with the genesis of various
arrhythmias, including ventricular tachycardia and atrial
fibrillation.
[0033] Baroreflex is a reflex triggered by stimulation of a
baroreceptor. A baroreceptor includes any sensor of pressure
changes, such as sensory nerve endings in the wall of the auricles
of the heart, vena cava, aortic arch and carotid sinus, that is
sensitive to stretching of the wall resulting from increased
pressure from within, and that functions as the receptor of the
central reflex mechanism that tends to reduce that pressure.
Clusters of nerve cells can be referred to as autonomic ganglia.
These nerve cells can also be electrically stimulated to induce a
baroreflex, which inhibits the sympathetic nerve activity and
stimulates parasympathetic nerve activity. Autonomic ganglia thus
forms part of a baroreflex pathway. Afferent nerve trunks, such as
the vagus, aortic and carotid nerves, leading from the sensory
nerve endings also form part of a baroreflex pathway. Stimulating a
baroreflex pathway and/or baroreceptors inhibits sympathetic nerve
activity (stimulates the parasympathetic nervous system) and
reduces systemic arterial pressure by decreasing peripheral
vascular resistance and cardiac contractility. Baroreceptors are
naturally stimulated by internal pressure and the stretching of
vessel wall (e.g. arterial wall).
[0034] Stimulating the sympathetic and parasympathetic nervous
systems can have effects other than heart rate and blood pressure.
For example, stimulating the sympathetic nervous system dilates the
pupil, reduces saliva and mucus production, relaxes the bronchial
muscle, reduces the successive waves of involuntary contraction
(peristalsis) of the stomach and the motility of the stomach,
increases the conversion of glycogen to glucose by the liver,
decreases urine secretion by the kidneys, and relaxes the wall and
closes the sphincter of the bladder. Stimulating the
parasympathetic nervous system (inhibiting the sympathetic nervous
system) constricts the pupil, increases saliva and mucus
production, contracts the bronchial muscle, increases secretions
and motility in the stomach and large intestine, and increases
digestion in the small intention, increases urine secretion, and
contracts the wall and relaxes the sphincter of the bladder. The
functions associated with the sympathetic and parasympathetic
nervous systems are many and can be complexly integrated with each
other.
[0035] Neural stimulation can be used to stimulate nerve traffic or
inhibit nerve traffic. An example of neural stimulation to
stimulate nerve traffic is a lower frequency signal (e.g. within a
range on the order of 20 Hz to 50 Hz). An example of neural
stimulation to inhibit nerve traffic is a higher frequency signal
(e.g. within a range on the order of 120 Hz to 150 Hz). Other
methods for stimulating and inhibiting nerve traffic have been
proposed, including anodal block of nerve traffic. According to
various embodiments of the present subject matter, sympathetic
neural targets include, but are not limited to, a peroneal nerve, a
sympathetic column in a spinal cord, and cardiac post-ganglionic
sympathetic neurons. The physical conditioning therapy can be
accomplished by stimulating neural activity at a sympathetic neural
target. According to various embodiments of the present subject
matter, parasympathetic neural targets include, but are not limited
to, a vagus nerve, a baroreceptor, and a cardiac fat pad. The
physical conditioning therapy can be accomplished by inhibiting
neural activity at a parasympathetic neural target.
Heart Failure
[0036] Heart failure refers to a clinical syndrome in which cardiac
function causes a below normal cardiac output that can fall below a
level adequate to meet the metabolic demand of peripheral tissues.
Heart failure may present itself as congestive heart failure (CHF)
due to the accompanying venous and pulmonary congestion. Heart
failure can be due to a variety of etiologies such as ischemic
heart disease. Heart failure patients have reduced autonomic
balance, which is associated with LV dysfunction and increased
mortality. Modulation of the sympathetic and parasympathetic
nervous systems has potential clinical benefit in preventing
remodeling and death in heart failure and post-MI patients. Direct
electrical stimulation can activate the baroreflex, inducing a
reduction of sympathetic nerve activity and reducing blood pressure
by decreasing vascular resistance. Sympathetic inhibition and
parasympathetic activation have been associated with reduced
arrhythmia vulnerability following a myocardial infarction,
presumably by increasing collateral perfusion of the acutely
ischemic myocardium and decreasing myocardial damage.
Hypertension
[0037] Hypertension is a cause of heart disease and other related
cardiac co-morbidities. Hypertension occurs when blood vessels
constrict. As a result, the heart works harder to maintain flow at
a higher blood pressure, which can contribute to heart failure.
Hypertension generally relates to high blood pressure, such as a
transitory or sustained elevation of systemic arterial blood
pressure to a level that is likely to induce cardiovascular damage
or other adverse consequences. Hypertension has been arbitrarily
defined as a systolic blood pressure above 140 mm Hg or a diastolic
blood pressure above 90 mm Hg. Consequences of uncontrolled
hypertension include, but are not limited to, retinal vascular
disease and stroke, left ventricular hypertrophy and failure,
myocardial infarction, dissecting aneurysm, and renovascular
disease.
[0038] A large segment of the general population, as well as a
large segment of patients implanted with pacemakers or
defibrillators, suffer from hypertension. The long term mortality
as well as the quality of life can be improved for this population
if blood pressure and hypertension can be reduced. Many patients
who suffer from hypertension do not respond to treatment, such as
treatments related to lifestyle changes and hypertension drugs.
Cardiac Remodeling
[0039] Following myocardial infarction (MI) or other cause of
decreased cardiac output, a complex remodeling process of the
ventricles occurs that involves structural, biochemical,
neurohormonal, and electrophysiologic factors. Ventricular
remodeling is triggered by a physiological compensatory mechanism
that acts to increase cardiac output due to so-called backward
failure which increases the diastolic filling pressure of the
ventricles and thereby increases the so-called preload (i.e., the
degree to which the ventricles are stretched by the volume of blood
in the ventricles at the end of diastole). An increase in preload
causes an increase in stroke volume during systole, a phenomena
known as the Frank-Starling principle. When the ventricles are
stretched due to the increased preload over a period of time,
however, the ventricles become dilated. The enlargement of the
ventricular volume causes increased ventricular wall stress at a
given systolic pressure. Along with the increased pressure-volume
work done by the ventricle, this acts as a stimulus for hypertrophy
of the ventricular myocardium. The disadvantage of dilatation is
the extra workload imposed on normal, residual myocardium and the
increase in wall tension (Laplace's Law) which represent the
stimulus for hypertrophy. If hypertrophy is not adequate to match
increased tension, a vicious cycle ensues which causes further and
progressive dilatation.
[0040] As the heart begins to dilate, afferent baroreceptor and
cardiopulmonary receptor signals are sent to the vasomotor central
nervous system control center, which responds with hormonal
secretion and sympathetic discharge. It is the combination of
hemodynamic, sympathetic nervous system and hormonal alterations
(such as presence or absence of angiotensin converting enzyme (ACE)
activity) that ultimately account for the deleterious alterations
in cell structure involved in ventricular remodeling. The sustained
stresses causing hypertrophy induce apoptosis (i.e., programmed
cell death) of cardiac muscle cells and eventual wall thinning
which causes further deterioration in cardiac function. Thus,
although ventricular dilation and hypertrophy may at first be
compensatory and increase cardiac output, the processes ultimately
result in both systolic and diastolic dysfunction. It has been
shown that the extent of ventricular remodeling is positively
correlated with increased mortality in post-MI and heart failure
patients.
Therapies
[0041] The present subject matter relates to systems, devices and
methods for providing physical conditioning using sympathetic
stimulation and/or parasympathetic inhibition. Various embodiments
provide a stand-alone device, either externally or internally, to
provide physical conditioning. Various embodiments provide systems
or devices that integrate physical conditioning therapy with one or
more other therapies, such as bradycardia pacing, anti-tachycardia
therapy, remodeling therapy, and the like.
Physical Conditioning Therapy
[0042] It is generally accepted that physical activity and fitness
improve health and reduce mortality. Studies have indicated that
aerobic training improves cardiac autonomic regulation, reduces
heart rate and is associated with increased cardiac vagal outflow.
A baseline measurement of higher parasympathetic activity is
associated with improved aerobic fitness. Exercise training
intermittently stresses the system and increases the sympathetic
activity during the stress. However, when an exercise session ends
and the stress is removed, the body rebounds in a manner that
increases baseline parasympathetic activity and reduces baseline
sympathetic activity.
[0043] Physical training stimulates the .beta..sub.1-receptors of
cardiac myocytes, which is a result of sympathetic stimulation.
Short periods of exercise (e.g. less than 1-2 hours) result in an
increase of .beta..sub.1-receptor activity. On the other hand,
periods of exercise longer than 2 hours can cause a reduction in
.beta..sub.1-receptor activity. Physical conditioning can be
considered to be a repetitive, high-level exercise that occurs
intermittently over time. The present subject matter mimics the
effects of physical conditioning with sympathetic nerve stimulation
and/or parasympathetic nerve inhibition.
[0044] FIG. 1 illustrates a method for providing physical
conditioning, according to various embodiments of the present
subject matter. A neural stimulator (understood to include devices
that apply electrical stimulation that stimulates nerve traffic
and/or inhibits nerve traffic) is turned on or otherwise enabled at
101. At 102, the device stimulates a sympathetic neural target,
inhibits a parasympathetic neural target, or both stimulates a
sympathetic neural target and inhibits a parasympathetic neural
target. At 103, the device is turned off or otherwise disables the
neural stimulator. In various external device embodiments, for
example, the device includes a switch capable of being actuated by
the patient or other person (e.g. physician) to turn the external
device on and off. In various internal device embodiments, for
example, the device is turned on and off through a wireless link
Examples of such wireless links include a magnetic field, and
communications through induction, RF or ultrasound. Various
embodiments provide user-initiated physical conditioning therapy
(e.g. 101 in FIG. 1), where a user "turns on" the therapy, which
runs for a preprogrammed time. Various embodiments provide
user-terminated physical conditioning therapy (e.g. 103 in FIG. 1),
where a programmed therapy is prematurely terminated by the user,
regardless of whether the user initiated the physical conditioning
therapy. Various embodiments provide user-titrated physical
conditioning therapy, where the intensity and/or duration of the
physical conditioning therapy can be increased or decreased by the
user. The user can be a patient, a physician or other person. These
user-initiated, user-terminated, and user-titrated embodiments can
be internal or external devices. Various embodiments provide the
ability for a user to perform all three functions (initiate,
terminate and titrate), or any combination of two or more of these
functions. An internal device embodiment uses an internal timer to
turn the device on (e.g. 101 in FIG. 1) and off (e.g. 103 in FIG.
1). A pre-programmed schedule can control the on-time and off-time
of the therapy. Other events can be used to either enable or
disable the programmed on-time and off-time. For example, the
programmed therapy can be enabled if the heart rate is within a
predetermined zone, if the systolic blood pressure is within a
predetermined zone, and/or the respiration rate is within a
predetermined zone. A programmed therapy can be disabled or
terminated if the heart rate is over a predetermined threshold, the
systolic blood pressure is over a predetermined threshold, and/or
the respiration rate is over a predetermined threshold.
[0045] FIG. 2 illustrates a method for providing physical
conditioning, according to various embodiments of the present
subject matter. At 204, it is determined whether a trigger has been
received to begin physical conditioning. When the trigger is
detected, a sympathetic neural target is stimulated and/or a
parasympathetic neural target is inhibited at 205. At 206, it is
determined whether a trigger to end the physical conditioning has
been received. Various implantable device embodiments are triggered
(e.g. 204 and 206) by an external signal controlled by a physician
or patient. A device embodiment uses a timer to turn the device on
(e.g. 204 in FIG. 2) and off (e.g. 206 in FIG. 2). A pre-programmed
schedule can control the on-time and off-time of the therapy. Other
events can be used to either enable or disable the programmed
on-time and off-time. Various sensor feedback can be used to enable
and/or disable the therapy. For example, the programmed therapy can
be enabled if the heart rate is within a predetermined zone, if the
systolic blood pressure is within a predetermined zone, and/or the
respiration rate is within a predetermined zone. A programmed
therapy can be disabled or terminated if the heart rate is over a
predetermined threshold, the systolic blood pressure is over a
predetermined threshold, and/or the respiration rate is over a
predetermined threshold. If the trigger to end the therapy has not
been received, it is determined at 207 whether to adjust the neural
stimulation parameters to achieve a target response for the
conditioning therapy. Adjustable neural stimulation parameters
include, but are not limited to, a stimulation duration as well as
an amplitude, frequency, pulse width, morphology, and burst
frequency of the neural stimulation signal. These parameters can be
appropriately increased or decreased to obtain a desired change in
the intensity of the neural stimulation/inhibition. Examples of
target responses include a target heart rate range or target blood
pressure range or respiratory rate for a period of time. If it is
determined at 207 to adjust the parameters, the process proceeds to
208 to adjust the parameter(s) and returns to 205; and if it is
determined that the parameters will not be adjusted, the process
returns from 207 to 205. Various embodiments provide target
range(s) as programmable parameters, and various embodiments
automatically adjust the intensity of the neural
stimulation/inhibition to maintain a sensed physiological parameter
(e.g. heart rate) within the target range. Various embodiments
provide means for manually adjusting the intensity based on a
sensed physiological parameter.
[0046] The physical conditioning therapy provided by the present
subject matter can be applied as therapy for heart failure. The
present subject matter stimulates a sympathetic target, inhibits a
parasympathetic target, or both stimulates a sympathetic target and
inhibits a parasympathetic target. The neural stimulation can be
provided using electrical, acoustic, ultrasound, light, and
magnetic therapies.
[0047] Examples of other physical conditioning therapies include
therapies for patients who are unable to exercise. For example,
physical conditioning using sympathetic stimulation/parasympathetic
inhibition for a bed-bound, post-surgical patient in a hospital may
enable the patient to maintain strength and endurance until such
time that the patient is able to exercise again. By way of another
example, a morbidly obese patient may be unable to exercise, but
may still benefit from the physical conditioning therapy.
Furthermore, patients with injuries such as joint injuries that
prevent them from performing their normal physical activities may
benefit from the physical conditioning therapy.
[0048] The physical conditioning therapy using sympathetic
stimulation and/or parasympathetic inhibition can be combined with
other therapies. Examples of such therapies include, but are not
limited to, CRM functions such as bradycardia pacing and
anti-tachycardia therapies, and cardiac resynchronization therapy,
and further include neural stimulation therapy such as hypertension
therapy, and remodeling therapy. These therapies are briefly
discussed below.
Bradycardia Pacing/CRT Pacing
[0049] A pacemaker is a device which paces the heart with timed
pacing pulses, most commonly for the treatment of bradycardia where
the ventricular rate is too slow. Atrio-ventricular conduction
defects (i.e., AV block) and sick sinus syndrome represent the most
common causes of bradycardia for which permanent pacing may be
indicated. If functioning properly, the pacemaker makes up for the
heart's inability to pace itself at an appropriate rhythm in order
to meet metabolic demand by enforcing a minimum heart rate.
[0050] Implantable devices have also been developed that affect the
manner and degree to which the heart chambers contract during a
cardiac cycle in order to promote the efficient pumping of blood.
The heart pumps more effectively when the chambers contract in a
coordinated manner, a result normally provided by the specialized
conduction pathways in both the atria and the ventricles that
enable the rapid conduction of excitation (i.e., depolarization)
throughout the myocardium. These pathways conduct excitatory
impulses from the sino-atrial node to the atrial myocardium, to the
atrio-ventricular node, and thence to the ventricular myocardium to
result in a coordinated contraction of both atria and both
ventricles. This both synchronizes the contractions of the muscle
fibers of each chamber and synchronizes the contraction of each
atrium or ventricle with the contralateral atrium or ventricle.
Without the synchronization afforded by the normally functioning
specialized conduction pathways, the heart's pumping efficiency is
greatly diminished. Pathology of these conduction pathways and
other inter-ventricular or intra-ventricular conduction deficits
can be a causative factor in heart failure, which refers to a
clinical syndrome in which an abnormality of cardiac function
causes cardiac output to fall below a level adequate to meet the
metabolic demand of peripheral tissues. In order to treat these
problems, implantable cardiac devices have been developed that
provide appropriately timed electrical stimulation to one or more
heart chambers in an attempt to improve the coordination of atrial
and/or ventricular contractions, termed cardiac resynchronization
therapy (CRT). Ventricular resynchronization is useful in treating
heart failure because, although not directly inotropic,
resynchronization can result in a more coordinated contraction of
the ventricles with improved pumping efficiency and increased
cardiac output. Currently, a common form of CRT applies stimulation
pulses to both ventricles, either simultaneously or separated by a
specified biventricular offset interval, and after a specified
atrio-ventricular delay interval with respect to the detection of
an intrinsic atrial contraction or delivery of an atrial pace.
Anti-Tachycardia Therapy
[0051] Cardioversion, an electrical shock delivered to the heart
synchronously with the QRS complex, and defibrillation, an
electrical shock delivered without synchronization to the QRS
complex, can be used to terminate most tachyarrhythmias. The
electric shock terminates the tachyarrhythmia by simultaneously
depolarizing the myocardium and rendering it refractory. A class of
CRM devices known as an implantable cardioverter defibrillator
(ICD) provides this kind of therapy by delivering a shock pulse to
the heart when the device detects tachyarrhythmias. Another type of
electrical therapy for tachycardia is anti-tachycardia pacing
(ATP). In ventricular ATP, the ventricles are competitively paced
with one or more pacing pulses in an effort to interrupt the
reentrant circuit causing the tachycardia. Modern ICDs typically
have ATP capability, and deliver ATP therapy or a shock pulse when
a tachyarrhythmia is detected.
Therapy for Cardiac Remodeling
[0052] CRT can be beneficial in reducing the deleterious
ventricular remodeling which can occur in post-MI and heart failure
patients. Presumably, this occurs as a result of changes in the
distribution of wall stress experienced by the ventricles during
the cardiac pumping cycle when CRT is applied. The degree to which
a heart muscle fiber is stretched before it contracts is termed the
preload, and the maximum tension and velocity of shortening of a
muscle fiber increases with increasing preload. When a myocardial
region contracts late relative to other regions, the contraction of
those opposing regions stretches the later contracting region and
increases the preload. The degree of tension or stress on a heart
muscle fiber as it contracts is termed the afterload. Because
pressure within the ventricles rises rapidly from a diastolic to a
systolic value as blood is pumped out into the aorta and pulmonary
arteries, the part of the ventricle that first contracts due to an
excitatory stimulation pulse does so against a lower afterload than
does a part of the ventricle contracting later. Thus a myocardial
region which contracts later than other regions is subjected to
both an increased preload and afterload. This situation is created
frequently by the ventricular conduction delays associated with
heart failure and ventricular dysfunction due to an MI. The
increased wall stress to the late-activating myocardial regions is
most probably the trigger for ventricular remodeling. By pacing one
or more sites in a ventricle near the infarcted region in a manner
which may cause a more coordinated contraction, CRT provides
pre-excitation of myocardial regions which would otherwise be
activated later during systole and experience increased wall
stress. The pre-excitation of the remodeled region relative to
other regions unloads the region from mechanical stress and allows
reversal or prevention of remodeling to occur.
Neural Stimulation Therapies
[0053] In addition to the electrical stimulation therapies
discussed above with respect to therapies for cardiac remodeling,
the physical conditioning of the present subject matter can be
integrated into a number of other neural stimulation therapies.
Examples of neural stimulation therapies include neural stimulation
therapies for respiratory problems such a sleep disordered
breathing, for blood pressure control such as to treat
hypertension, for cardiac rhythm management, for myocardial
infarction and ischemia, for heart failure, for epilepsy, for
depression, for pain, for migraines, for eating disorders and
obesity, and for movement disorders. Many proposed neural
stimulation therapies include parasympathetic stimulation through
stimulation of the vagus nerve and cardiac branches of the vagus
nerve. This listing of other neural stimulation therapies is not
intended to be an exhaustive listing.
[0054] FIG. 3 illustrates a physical conditioning therapy using
sympathetic stimulation and/or parasympathetic inhibition,
according to various embodiments of the present subject matter, and
FIGS. 4-5 illustrate examples of therapy protocols that combine or
integrate sympathetic stimulation and/or parasympathetic inhibition
associated with physical conditioning with therapies that use
parasympathetic stimulation and/or sympathetic inhibition,
according to various embodiments of the present subject matter. The
time line is divided into 24 intervals, such as may be used to
illustrate hours in a day. The illustrated therapies on the time
line are intended as an example. Other therapy regimens can be
implemented. In FIG. 3, it is illustrated that a physical
conditioning therapy is applied for a short duration. This therapy
is applied intermittently in some embodiments. Some embodiments
apply the physical conditioning in a periodic manner (e.g. daily or
every other day). For example, some embodiments apply the
stimulation to mimic an exercise regimen (e.g. walk 5 times per
week for 30 minutes and maintain a heart rate within a target
range). Various embodiments provide the total therapy for the day
(e.g. 30 minutes per day) in increments (e.g. 5 minutes of therapy
provided 6 times per day) The physical conditioning involves
sympathetic stimulation, parasympathetic inhibition, or both
sympathetic stimulation and parasympathetic inhibition to
intermittently stress the patient. In contrast, an
anti-hypertension therapy, for example, applies parasympathetic
stimulation, sympathetic inhibition, or both parasympathetic
stimulation and sympathetic inhibition. The anti-hypertension
therapy can be applied intermittently or periodically (e.g. 5
minutes every hour or 5 seconds every minute). As illustrated
generally in FIG. 4, the application of the physical conditioning
is timed to occur between anti-hypertension therapy. An
anti-remodeling therapy also applies parasympathetic stimulation,
sympathetic inhibition, or both parasympathetic stimulation and
sympathetic inhibition. The anti-remodeling therapy can be provided
on a more continuous basis. As illustrated generally in FIG. 5, the
anti-remodeling therapy can be interrupted to provide a window of
time in which to provide the physical conditioning therapy. Some
embodiments are able to provide parasympathetic stimulation and
inhibition at the same site selectable by varying, for example, the
frequency of stimulation or polarity of stimulation. Some
embodiments are able to provide sympathetic stimulation and
inhibition at the same site selectable by varying, for example, the
frequency of stimulation or polarity of stimulation. Some
embodiments are able to simultaneously provide a local
parasympathetic response at a first location and a local
sympathetic response in another location.
Hypertension
[0055] One neural stimulation therapy involves treating
hypertension by stimulating the baroreflex for sustained periods of
time sufficient to reduce hypertension. The baroreflex is a reflex
that can be triggered by stimulation of a baroreceptor or an
afferent nerve trunk. Baroreflex neural targets include any sensor
of pressure changes, such as sensory nerve endings in the wall of
the auricles of the heart, cardiac fat pads, vena cava, aortic arch
and carotid sinus, that is sensitive to stretching of the wall
resulting from increased pressure from within, and that functions
as the receptor of the central reflex mechanism that tends to
reduce that pressure. Examples of afferent nerve trunks that can
serve as baroreflex neural targets include the vagus, aortic and
carotid nerves. Stimulating baroreceptors inhibits sympathetic
nerve activity (stimulates the parasympathetic nervous system) and
reduces systemic arterial pressure by decreasing peripheral
vascular resistance and cardiac contractility. Baroreceptors are
naturally stimulated by internal pressure and the stretching of the
arterial wall. Some aspects of the present subject matter locally
stimulate specific nerve endings in arterial walls rather than
stimulate afferent nerve trunks in an effort to stimulate a desire
response (e.g. reduced hypertension) while reducing the undesired
effects of indiscriminate stimulation of the nervous system. For
example, some embodiments stimulate baroreceptor sites in the
pulmonary artery. Some embodiments of the present subject matter
involve stimulating either baroreceptor sites or nerve endings in
the aorta, the chambers of the heart, the fat pads of the heart,
and some embodiments of the present subject matter involve
stimulating an afferent nerve trunk, such as the vagus, carotid and
aortic nerves. Some embodiments stimulate afferent nerve trunks
using a cuff electrode, and some embodiments stimulate afferent
nerve trunks using an intravascular lead positioned in a blood
vessel proximate to the nerve, such that the electrical stimulation
passes through the vessel wall to stimulate the afferent nerve
trunk.
Neural Stimulation for Ventricular Remodeling
[0056] Another therapy involves preventing and/or treating
ventricular remodeling. Activity of the autonomic nervous system is
at least partly responsible for the ventricular remodeling which
occurs as a consequence of an MI or due to heart failure. It has
been demonstrated that remodeling can be affected by
pharmacological intervention with the use of, for example, ACE
inhibitors and beta-blockers. Pharmacological treatment carries
with it the risk of side effects, however, and it is also difficult
to modulate the effects of drugs in a precise manner. Embodiments
of the present subject matter employ electrostimulatory means to
modulate autonomic activity, referred to as anti-remodeling therapy
or ART. When delivered in conjunction with ventricular
resynchronization pacing, also referred to as remodeling control
therapy (RCT), such modulation of autonomic activity acts
synergistically to reverse or prevent cardiac remodeling.
[0057] Increased sympathetic nervous system activity following
ischemia often results in increased exposure of the myocardium to
epinephrine and norepinephrine. These catecholamines activate
intracellular pathways within the myocytes, which lead to
myocardial death and fibrosis. Stimulation of the parasympathetic
nerves (vagus) inhibits this effect. According to various
embodiments, the present subject matter selectively activates the
vagal cardiac nerves in addition to CRT in heart failure patients
to protect the myocardium from further remodeling and
arrhythmogenesis. Other potential benefits of stimulating vagal
cardiac nerves in addition to CRT include reducing inflammatory
response following myocardial infarction, and reducing the
electrical stimulation threshold for defibrillating. For example,
when a ventricular tachycardia is sensed, vagal nerve stimulation
is applied, and then a defibrillation shock is applied. The vagal
nerve stimulation allows the defibrillation shock to be applied at
less energy. Also, parasympathetic stimulation may terminate an
arrhythmia or otherwise increase the effectiveness of an
anti-arrhythmia treatment.
[0058] As illustrated in FIGS. 6A and 6B, the heart 609 includes a
superior vena cava 610, an aortic arch 611, and a pulmonary artery
612. CRM leads 613 pass nerve sites that can be stimulated in
accordance with the present subject matter. FIG. 6A illustrates
transvascularly fed leads, and FIG. 6B illustrates epicardial
leads. Examples of electrode positions are provided in the drawings
by the symbol "X". For example, CRM leads are capable of being
intravascularly inserted through a peripheral vein and into the
coronary sinus, and are capable of being intravascularly inserted
through a peripheral vein and through the tricuspid valve into the
right ventricle of the heart (not expressly shown in the figure)
similar to a cardiac pacemaker lead, and continue from the right
ventricle through the pulmonary valve into the pulmonary artery.
The coronary sinus and pulmonary artery are provided as examples of
vasculature proximate to the heart in which a lead can be
intravascularly inserted to stimulate nerves within or proximate to
the vasculature. Thus, according to various aspects of the present
subject matter, nerves are stimulated in or around vasculature
located proximate to the heart by at least one electrode
intravascularly inserted therein.
[0059] FIGS. 7A and 7B illustrate the right side and left side of
the heart, respectively, and further illustrate cardiac fat pads
which provide neural targets for some neural stimulation therapies.
FIG. 7A illustrates the right atrium 714, right ventricle 715,
sinoatrial node 716, superior vena cava 710, inferior vena cava
717, aorta 718, right pulmonary veins 719, and right pulmonary
artery 720. FIG. 7A also illustrates a cardiac fat pad 721 between
the superior vena cava and aorta. Neural targets in the cardiac fat
pad 721 are stimulated in some embodiments using an electrode
screwed into or otherwise placed in the fat pad, and are stimulated
in some embodiments using an intravenously-fed lead proximately
positioned to the fat pad in a vessel such as the right pulmonary
artery or superior vena cava, for example. FIG. 7B illustrates the
left atrium 722, left ventricle 723, right atrium 714, right
ventricle 715, superior vena cava 710, inferior vena cava 717,
aorta 718, right pulmonary veins 719, left pulmonary vein 724,
right pulmonary artery 720, and coronary sinus 725. FIG. 7B also
illustrates a cardiac fat pad 726 located proximate to the right
cardiac veins and a cardiac fat pad 727 located proximate to the
inferior vena cava and left atrium. Neural targets in the fat pad
726 are stimulated in some embodiments using an electrode screwed
into the fat pad 726, and are stimulated in some embodiments using
an intravenously-fed lead proximately positioned to the fat pad in
a vessel such as the right pulmonary artery 720 or right pulmonary
vein 719, for example. Neural targets in the fat pad 727 are
stimulated in some embodiments using an electrode screwed into the
fat pad, and are stimulated in some embodiments using an
intravenously-fed lead proximately positioned to the fat pad in a
vessel such as the inferior vena cava 717 or coronary sinus or a
lead in the left atrium 722, for example.
[0060] Various lead embodiments implement a number of designs,
including an expandable stent-like electrode with a mesh surface
dimensioned to abut a wall of a predetermined blood vessel, a
coiled electrode(s), a fixed screw-type electrode(s), and the like.
Various embodiments place the electrode(s) inside the blood vessel,
into the wall of the blood vessel, or a combination of at least one
electrode inside the blood vessel and at least one electrode into
the wall of the blood vessel. The neural stimulation electrode(s)
can be integrated into the same lead used for CRT or in another
lead in addition to CRT lead(s).
[0061] Intravascularly-fed leads adapted to transvascularly
stimulate a target outside of the vessel, also referred to herein
as transvascular leads, can be used to stimulate other nerve sites.
For example, an embodiment feeds a transvascular stimulation lead
into the right azygos vein to stimulate and/or inhibit nerve
traffic on the vagus nerve; and an embodiment feeds a transvascular
stimulation lead into the internal jugular vein to stimulate and/or
inhibit nerve traffic on the vagus nerve. Various embodiments use
at least one lead intravascularly fed along a lead path to
transvascularly apply neural stimulation and electrically stimulate
a cardiac muscle, such as ventricular pacing, as part of CRT.
[0062] Other transvascular locations have been mentioned with
respect to FIGS. 7A and 7B. Depending on the intravascular location
of the neural stimulation electrode(s), the right vagal branch, the
left vagal branch or a combination of the right and left vagal
branches are capable of being stimulated. The left and right vagal
branches innervate different areas of the heart, and thus provide
different results when stimulated. According to present knowledge,
the right vagus nerve appears to innervate the right side of the
heart, including the right atrium and right ventricle, and the left
vagus nerve appears to innervate the left side of the heart,
including the left atrium and left ventricle. Stimulation of the
right vagus has more chronotropic effects because the sinus node is
on the right side of the heart. Thus, various embodiments
selectively stimulate the right vagus nerve and/or the left vagus
nerve to selectively control contractility, excitability, and
inflammatory response on the right and/or left side of the heart.
Since the venous system is for the most part symmetrical, leads can
be fed into an appropriate vessel to transvascularly stimulate the
right or left vagus nerve. For example, a lead in the right
internal jugular vein can be used to stimulate the right vagus
nerve and a lead in the left internal jugular vein can be used to
stimulate the left vagus nerve.
[0063] The stimulation electrode(s) are not in direct neural
contact with the nerve when the transvascular approach to
peripheral nerve stimulation is used. Thus, problems associated
with neural inflammation and injury commonly associated with direct
contact electrodes are reduced.
Device Embodiments
[0064] FIG. 8 illustrates an implantable medical device (IMD) 830,
according to various embodiments of the present subject matter. The
illustrated IMD provides neural stimulation signals for delivery to
predetermined neural targets to provide physical conditioning
therapy. The illustrated device includes controller circuitry 831
and memory 832. The controller circuitry is capable of being
implemented using hardware, software, and combinations of hardware
and software. For example, according to various embodiments, the
controller circuitry includes a processor to perform instructions
embedded in the memory to perform functions associated with the
neural stimulation therapy. For example, the illustrated device
further includes a transceiver 833 and associated circuitry for use
to communicate with a programmer or another external or internal
device. Various embodiments have wireless communication
capabilities. For example, some transceiver embodiments use a
telemetry coil to wirelessly communicate with a programmer or
another external or internal device.
[0065] The illustrated device further includes neural stimulation
circuitry 834. Various embodiments of the device also includes
sensor circuitry 835. According to some embodiments, one or more
leads are able to be connected to the sensor circuitry and neural
stimulation circuitry. Some embodiments use wireless connections
between the sensor(s) and sensor circuitry, and some embodiments
use wireless connections between the stimulator circuitry and
electrodes. According to various embodiments, the neural
stimulation circuitry is used to apply electrical stimulation
pulses to desired neural targets, such as through one or more
stimulation electrodes 836 positioned at predetermined location(s).
Some embodiments use transducers to provide other types of energy,
such as ultrasound, light or magnetic energy. In various
embodiments, the sensor circuitry is used to detect physiological
responses. Examples of physiological responses include cardiac
activity, such as heart rate and minute ventilation, blood
pressure, and respiration, such as tidal volume and minute
ventilation. The controller circuitry can compare a target range
(or ranges) of the sensed physiological response(s) stored in the
memory to the sensed physiological response(s) to appropriately
adjust the intensity of the neural stimulation/inhibition.
[0066] According to various embodiments, the stimulation circuitry
834 is adapted to set or adjust any one or any combination of
stimulation features. Examples of stimulation features include the
amplitude, frequency, polarity and wave morphology of the
stimulation signal. Examples of wave morphology include a square
wave, triangle wave, sinusoidal wave, and waves with desired
harmonic components to mimic white noise such as is indicative of
naturally-occurring baroreflex stimulation. Some embodiments of the
neural stimulation circuitry 834 are adapted to generate a
stimulation signal with a predetermined amplitude, morphology,
pulse width and polarity, and are further adapted to respond to a
control signal from the controller to modify at least one of the
amplitude, wave morphology, pulse width and polarity. Some
embodiments of the neural stimulation circuitry 834 are adapted to
generate a stimulation signal with a predetermined frequency, and
are further adapted to respond to a control signal from the
controller to modify the frequency of the stimulation signal.
[0067] The controller 831 can be programmed to control the neural
stimulation delivered by the stimulation circuitry 834 according to
stimulation instructions, such as a stimulation schedule, stored in
the memory 832. Neural stimulation can be delivered in a
stimulation burst, which is a train of stimulation pulses at a
predetermined frequency. Stimulation bursts can be characterized by
burst durations and burst intervals. A burst duration is the length
of time that a burst lasts. A burst interval can be identified by
the time between the start of successive bursts. A programmed
pattern of bursts can include any combination of burst durations
and burst intervals. A simple burst pattern with one burst duration
and burst interval can continue periodically for a programmed
period or can follow a more complicated schedule. The programmed
pattern of bursts can be more complicated, composed of multiple
burst durations and burst interval sequences. The programmed
pattern of bursts can be characterized by a duty cycle, which
refers to a repeating cycle of neural stimulation ON for a fixed
time and neural stimulation OFF for a fixed time. Duty cycle is
specified by the ON time and the cycle time, and thus can have
units of ON time/cycle time. For example, if the ON/OFF cycle
repeats every 1 minute and the ON time of the duty cycle is 10
seconds, then the duty cycle is 10 seconds per minute. If the
ON/OFF cycle repeats every one hour and the ON time is 5 minutes,
then the duty cycle is 5 minutes per hour. According to some
embodiments, the controller 831 controls the neural stimulation
generated by the stimulation circuitry by initiating each pulse of
the stimulation signal. In some embodiments, the controller
circuitry initiates a stimulation signal pulse train, where the
stimulation signal responds to a command from the controller
circuitry by generating a train of pulses at a predetermined
frequency and burst duration. The predetermined frequency and burst
duration of the pulse train can be programmable. The pattern of
pulses in the pulse train can be a simple burst pattern with one
burst duration and burst interval or can follow a more complicated
burst pattern with multiple burst durations and burst intervals. In
some embodiments, the controller 831 controls the stimulation
circuitry 834 to initiate a neural stimulation session and to
terminate the neural stimulation session. The burst duration of the
neural stimulation session under the control of the controller 831
can be programmable. The controller may also terminate a neural
stimulation session in response to an interrupt signal, such as may
be generated by one or more sensed parameters or any other
condition where it is determined to be desirable to stop neural
stimulation.
[0068] The sensor circuitry is used to detect a physiological
response 890. The controller 831 compares the response 890 to a
target range stored in memory 832, and controls the neural
stimulation based on the comparison in an attempt to keep the
response 890 within the target range. The target range can be
programmable. The physiological response can include cardiac
activity 891, blood pressure 892, respiration 893, or various
combinations thereof. Examples of cardiac activity sensors include
heart rate and minute ventilation sensors. Examples of respiration
sensors include tidal volume and minute ventilation sensors.
[0069] The illustrated device includes a programmed physical
conditioning therapy schedule stored in memory 832 and further
includes a clock or timer 811 which can be used to execute the
programmable physical conditioning stimulation schedule. For
example, a physician can program a daily/weekly schedule of therapy
based on the time of day. A stimulation session can begin at a
first programmed time, and can end at a second programmed time.
Various embodiments initiate and/or terminate a stimulation session
based on a signal triggered by a user. Various embodiments use
sensed data to enable and/or disable a stimulation session.
[0070] According to various embodiments, the physical conditioning
schedule refers to the time intervals or period when the neural
stimulation therapy is delivered. A schedule can be defined by a
start time and an end time, or a start time and a duration. Various
schedules deliver therapy periodically. According to various
examples, a device can be programmed with a therapy schedule to
deliver therapy from midnight to 2AM every day, or to deliver
therapy for one hour every six hours, or to delivery therapy for
two hours per day, or according to a more complicated timetable.
Various device embodiments apply the therapy according to the
programmed schedule contingent on enabling conditions, such as
sensed exercise periods, patient rest or sleep, low heart rate
levels, and the like. The therapy schedule can also specify how the
stimulation is delivered, such as continuously at the pulse
frequency throughout the identified therapy period (e.g. 5 Hz pulse
frequency for one hour every day), or according to a defined duty
cycle during the therapy delivery period (e.g. 10 seconds per
minute at 5 Hz pulse frequency for one hour per day). As
illustrated by these examples, the therapy schedule is
distinguishable from the duty cycle.
[0071] FIG. 9 illustrates an implantable medical device (IMD) 941
having a neural stimulation (NS) component 942 and cardiac rhythm
management (CRM) component 943, according to various embodiments of
the present subject matter. The illustrated device includes a
controller 944 and memory 945. The illustrated memory 945 includes
a programmable physical conditioning therapy schedule. The
illustrated memory 945 also includes programmable physiological
response target(s) that can be used to enable and/or disable the
scheduled therapy or to otherwise provide feedback for the therapy.
According to various embodiments, the controller includes hardware,
software, or a combination of hardware and software to perform the
neural stimulation and CRM functions. For example, the programmed
therapy applications discussed in this disclosure are capable of
being stored as computer-readable instructions embodied in memory
and executed by a processor. According to various embodiments, the
controller includes a processor to execute instructions embedded in
memory to perform the neural stimulation and CRM functions. The
neural stimulation therapy includes physical conditioning. Other
examples of neural stimulation include anti-hypertension (AHT)
therapy and anti-remodeling therapy (ART). Examples of CRM
functions include bradycardia pacing, anti-tachycardia therapies
such as ATP, defibrillation and cardioversion, and CRT. The
controller also executes instructions to detect a tachyarrhythmia.
The illustrated device further includes a transceiver 946 and
associated circuitry for use to communicate with a programmer or
another external or internal device. Various embodiments include a
telemetry coil.
[0072] The CRM therapy section 943 includes components, under the
control of the controller, to stimulate a heart and/or sense
cardiac signals using one or more electrodes. The illustrated CRM
therapy section includes a pulse generator 947 for use to provide
an electrical signal through an electrode to stimulate a heart, and
further includes sense circuitry 948 to detect and process sensed
cardiac signals. An interface 949 is generally illustrated for use
to communicate between the controller 944 and the pulse generator
947 and sense circuitry 948. Three electrodes are illustrated as an
example for use to provide CRM therapy. However, the present
subject matter is not limited to a particular number of electrode
sites. Each electrode may include its own pulse generator and sense
circuitry. However, the present subject matter is not so limited.
The pulse generating and sensing functions can be multiplexed to
function with multiple electrodes.
[0073] The NS therapy section 942 includes components, under the
control of the controller, to stimulate a neural stimulation target
and/or sense parameters associated with nerve activity or
surrogates of nerve activity such as blood pressure and
respiration. Three interfaces 950 are illustrated for use to
provide neural stimulation. However, the present subject matter is
not limited to a particular number interfaces, or to any particular
stimulating or sensing functions. Pulse generators 951 are used to
provide electrical pulses to transducer or transducers for use to
stimulate a neural stimulation target. According to various
embodiments, the pulse generator includes circuitry to set, and in
some embodiments change, the amplitude of the stimulation pulse,
the frequency of the stimulation pulse, the burst frequency of the
pulse, and the morphology of the pulse such as a square wave,
triangle wave, sinusoidal wave, and waves with desired harmonic
components to mimic white noise or other signals. Sense circuits
952 are used to detect and process signals from a sensor, such as a
sensor of nerve activity, blood pressure, respiration, and the
like. The interfaces 950 are generally illustrated for use to
communicate between the controller 944 and the pulse generator 951
and sense circuitry 952. Each interface, for example, may be used
to control a separate lead. Various embodiments of the NS therapy
section only includes a pulse generator to stimulate a neural
target.
[0074] The illustrated device includes a clock or timer 911, which
can be used to execute a programmable physical conditioning
stimulation schedule. For example, a physician can program a
daily/weekly schedule of therapy based on the time of day. A
stimulation session can begin at a first programmed time, and can
end at a second programmed time. Various embodiments initiate
and/or terminate a stimulation session based on a signal triggered
by a user. Various embodiments use sensed data to enable and/or
disable a stimulation session.
[0075] FIG. 10 shows a system diagram of an embodiment of a
microprocessor-based implantable device, according to various
embodiments. The controller of the device is a microprocessor 1053
which communicates with a memory 1054 via a bidirectional data bus.
The controller could be implemented by other types of logic
circuitry (e.g., discrete components or programmable logic arrays)
using a state machine type of design, but a microprocessor-based
system is preferable. As used herein, the term "circuitry" should
be taken to refer to either discrete logic circuitry or to the
programming of a microprocessor. Shown in the figure are three
examples of sensing and pacing channels designated "A" through "C"
comprising bipolar leads with ring electrodes 1055A-C and tip
electrodes 1056A-C, sensing amplifiers 1057A-C, pulse generators
1058A-C, and channel interfaces 1059A-C. Each channel thus includes
a pacing channel made up of the pulse generator connected to the
electrode and a sensing channel made up of the sense amplifier
connected to the electrode. The channel interfaces 1059A-C
communicate bidirectionally with the microprocessor 1053, and each
interface may include analog-to-digital converters for digitizing
sensing signal inputs from the sensing amplifiers and registers
that can be written to by the microprocessor in order to output
pacing pulses, change the pacing pulse amplitude, and adjust the
gain and threshold values for the sensing amplifiers. The sensing
circuitry of the pacemaker detects a chamber sense, either an
atrial sense or ventricular sense, when an electrogram signal
(i.e., a voltage sensed by an electrode representing cardiac
electrical activity) generated by a particular channel exceeds a
specified detection threshold. Pacing algorithms used in particular
pacing modes employ such senses to trigger or inhibit pacing. The
intrinsic atrial and/or ventricular rates can be measured by
measuring the time intervals between atrial and ventricular senses,
respectively, and used to detect atrial and ventricular
tachyarrhythmias.
[0076] The electrodes of each bipolar lead are connected via
conductors within the lead to a switching network 1060 controlled
by the microprocessor. The switching network is used to switch the
electrodes to the input of a sense amplifier in order to detect
intrinsic cardiac activity and to the output of a pulse generator
in order to deliver a pacing pulse. The switching network also
enables the device to sense or pace either in a bipolar mode using
both the ring and tip electrodes of a lead or in a unipolar mode
using only one of the electrodes of the lead with the device
housing (can) 1061 or an electrode on another lead serving as a
ground electrode. A shock pulse generator 1062 is also interfaced
to the controller for delivering a defibrillation shock via a pair
of shock electrodes 1063 and 1064 to the atria or ventricles upon
detection of a shockable tachyarrhythmia.
[0077] Neural stimulation channels, identified as channels D and E,
are incorporated into the device for delivering parasympathetic
inhibition and/or stimulation and/or sympathetic stimulation and/or
inhibition, where one channel includes a bipolar lead with a first
electrode 1065D and a second electrode 1066D, a pulse generator
1067D, and a channel interface 1068D, and the other channel
includes a bipolar lead with a first electrode 1065E and a second
electrode 1066E, a pulse generator 1067E, and a channel interface
1068E. Other embodiments may use unipolar leads in which case the
neural stimulation pulses are referenced to the can or another
electrode. The pulse generator for each channel outputs a train of
neural stimulation pulses which may be varied by the controller as
to amplitude, frequency, duty-cycle, and the like. In this
embodiment, each of the neural stimulation channels uses a lead
which can be intravascularly disposed near an appropriate neural
target. Other types of leads and/or electrodes may also be
employed. A nerve cuff electrode may be used in place of an
intravascularly disposed electrode to provide neural stimulation.
In some embodiments, the leads of the neural stimulation electrodes
are replaced by wireless links.
[0078] The figure illustrates a telemetry interface 1069 connected
to the microprocessor, which can be used to communicate with an
external device. The illustrated microprocessor 1053 is capable of
performing neural stimulation therapy routines and myocardial
stimulation routines. Examples of NS therapy routines include
physical conditioning therapy (sympathetic stimulation and/or
parasympathetic inhibition), anti-hypertension therapy
(parasympathetic stimulation and/or sympathetic inhibition), and
anti-remodeling therapy (parasympathetic stimulation and/or
sympathetic inhibition). Examples of myocardial therapy routines
include bradycardia pacing therapies, anti-tachycardia shock
therapies such as cardioversion or defibrillation therapies,
anti-tachycardia pacing therapies, and cardiac resynchronization
therapies.
System Embodiments
[0079] FIG. 11 illustrates a system 1170 including an implantable
medical device (IMD) 1171 and an external system or device 1172,
according to various embodiments of the present subject matter.
Various embodiments of the IMD include a combination of NS and CRM
functions. The IMD may also deliver biological agents and
pharmaceutical agents. The external system and the IMD are capable
of wirelessly communicating data and instructions. In various
embodiments, for example, the external system and IMD use telemetry
coils to wirelessly communicate data and instructions. Thus, the
programmer can be used to adjust the programmed therapy provided by
the IMD, and the IMD can report device data (such as battery and
lead resistance) and therapy data (such as sense and stimulation
data) to the programmer using radio telemetry, for example.
According to various embodiments, the IMD stimulates/inhibits a
neural target to provide a physical conditioning therapy.
[0080] The external system allows a user such as a physician or
other caregiver or a patient to control the operation of the IMD
and obtain information acquired by the IMD. In one embodiment,
external system includes a programmer communicating with the IMD
bi-directionally via a telemetry link. In another embodiment, the
external system is a patient management system including an
external device communicating with a remote device through a
telecommunication network. The external device is within the
vicinity of the IMD and communicates with the IMD bi-directionally
via a telemetry link. The remote device allows the user to monitor
and treat a patient from a distant location. The patient monitoring
system is further discussed below.
[0081] The telemetry link provides for data transmission from
implantable medical device to external system. This includes, for
example, transmitting real-time physiological data acquired by IMD,
extracting physiological data acquired by and stored in IMD,
extracting therapy history data stored in implantable medical
device, and extracting data indicating an operational status of the
IMD (e.g., battery status and lead impedance). Telemetry link also
provides for data transmission from external system to IMD. This
includes, for example, programming the IMD to acquire physiological
data, programming IMD to perform at least one self-diagnostic test
(such as for a device operational status), and programming the IMD
to deliver at least one therapy.
[0082] FIG. 12 illustrates a system 1270 including an external
device 1272, an implantable neural stimulator (NS) device 1273 and
an implantable cardiac rhythm management (CRM) device 1274,
according to various embodiments of the present subject matter.
Various aspects involve a method for communicating between an NS
device and a CRM device or other cardiac stimulator. In various
embodiments, this communication allows one of the devices 1273 or
1274 to deliver more appropriate therapy (i.e. more appropriate NS
therapy or CRM therapy) based on data received from the other
device. Some embodiments provide on-demand communications. In
various embodiments, this communication allows each of the devices
to deliver more appropriate therapy (i.e. more appropriate NS
therapy and CRM therapy) based on data received from the other
device. The illustrated NS device and the CRM device are capable of
wirelessly communicating with each other, and the external system
is capable of wirelessly communicating with at least one of the NS
and the CRM devices. For example, various embodiments use telemetry
coils to wirelessly communicate data and instructions to each
other. In other embodiments, communication of data and/or energy is
by ultrasonic means. Rather than providing wireless communication
between the NS and CRM devices, various embodiments provide a
communication cable or wire, such as an intravenously-fed lead, for
use to communicate between the NS device and the CRM device. In
some embodiments, the external system functions as a communication
bridge between the NS and CRM devices.
[0083] Various embodiments target cardiac post-ganglionic neurons,
which can be stimulated from a position near the sympathetic
ganglia along the spinal cord or from a position over the
sympathetic nerve plexus (network) innervating the heart. The
sympathetic nerve plexus innervating the heart can be accessed, for
example from within a coronary vein overlying a concentration of
cardiac sympathetic nerve endings, or in the superior vena cava or
pulmonary artery proximate to the cardiac plexus, or in the right
atrium septal wall or right ventricle septal wall. According to
various embodiments, the design and placement of the neural
stimulation electrodes and the stimulation parameters are selected
to preferentially stimulate the cardiac neural network and avoid
stimulating the myocardium. This preferential neural stimulation
may include current field steering designs and methods. Various
embodiments synchronize the neural stimulation to the heart rate so
that the neural stimulation is triggered to start when the
neighboring myocardium is first activated (depolarized) and to last
to the end of the refractory period for that myocardium. The end of
the refractory period can be a predetermined duration based on
typical myocardia refractory times or can be measured by sensing
the T-wave of the ECG. The heart rate and T-wave (ECG) can be
sensed using a leadless ECG on the can of the implantable medical
device, or a lead from the neural stimulator implanted in a chamber
of the heart (e.g. right atrium) or a wireless connection to a
co-implanted CRM device that is monitoring heart rate and
communicating it to the neural stimulator via a wireless link.
[0084] FIG. 13 illustrates an IMD 1375 placed subcutaneously or
submuscularly in a patient's chest with a lead 1376 positioned to
provide cardiac post-ganglionic sympathetic nerve plexus
stimulation, and with a lead 1377 positioned to stimulate and/or
inhibit neural traffic in a vagus nerve, by way of example and not
by way of limitation, according to various embodiments. Various
embodiments include leads to provide a desired CRM therapy.
According to various embodiments, neural stimulation lead(s) 1377
are subcutaneously tunneled to a neural target, and can have a
nerve cuff electrode to stimulate the neural target. Some lead
embodiments are intravascularly fed into a vessel proximate to the
neural target, and use transducer(s) within the vessel to
transvascularly stimulate the neural target. For example, some
embodiments stimulate/inhibit the vagus nerve using electrode(s)
positioned within the internal jugular vein.
[0085] FIG. 14 illustrates an IMD 1475 with a lead 1476 positioned
to provide cardiac post-ganglionic sympathetic nerve plexus
stimulation, and with satellite transducers 1477A and 1477B
positioned to stimulate/inhibit a neural target, according to
various embodiments. Transducer 1477A is positioned to
stimulate/inhibit the vagus nerve. Transducer 1477B is positioned
to stimulate spinal cord sympathetic ganglia. The satellite
transducers are connected to the IMD, which functions as the planet
for the satellites, via a wireless link. Stimulation and
communication can be performed through the wireless link. Examples
of wireless links include RF links and ultrasound links. Although
not illustrated, some embodiments perform cardiac post-ganglionic
sympathetic nerve plexus stimulation using wireless links. Examples
of satellite transducers include subcutaneous electrodes, nerve
cuff electrodes and intravascular electrodes. Some embodiments
stimulate/inhibit the vagus nerve using electrode(s) positioned
within the internal jugular vein.
[0086] FIG. 15 illustrates a leg, and further illustrates a nerve
stimulator 1579 adapted to stimulate a peroneal nerve 1578 in the
leg. Various embodiments provide an external neural stimulator,
which can be placed behind the knee to stimulate the peroneal nerve
and elicit a sympathetic response. Some device embodiments provide
an implantable device that can be positioned to stimulate the
peroneal nerve. The electrodes or transducers used to stimulate the
peroneal nerve can be powered and controlled through a wireless
connection or through a tethered connection.
[0087] FIG. 16 is a block diagram illustrating an embodiment of an
external system 1680. The external system includes a programmer, in
some embodiments. In the illustrated embodiment, the external
system includes a patient management system. As illustrated,
external system 1680 is a patient management system including an
external device 1681, a telecommunication network 1682, and a
remote device 1683. External device 1681 is placed within the
vicinity of an IMD and includes external telemetry system 1684 to
communicate with the IMD. Remote device(s) 1683 is in one or more
remote locations and communicates with external device 1681 through
network 1682, thus allowing a physician or other caregiver to
monitor and treat a patient from a distant location and/or allowing
access to various treatment resources from the one or more remote
locations. The illustrated remote device 1683 includes a user
interface 1685.
[0088] One of ordinary skill in the art will understand that the
modules and other circuitry shown and described herein can be
implemented using software, hardware, and combinations of software
and hardware. As such, the term module is intended to encompass
software implementations, hardware implementations, and software
and hardware implementations.
[0089] The methods illustrated in this disclosure are not intended
to be exclusive of other methods within the scope of the present
subject matter. Those of ordinary skill in the art will understand,
upon reading and comprehending this disclosure, other methods
within the scope of the present subject matter. The
above-identified embodiments, and portions of the illustrated
embodiments, are not necessarily mutually exclusive. These
embodiments, or portions thereof, can be combined. In various
embodiments, the methods provided above are implemented as a
computer data signal embodied in a carrier wave or propagated
signal, that represents a sequence of instructions which, when
executed by a processor cause the processor to perform the
respective method. In various embodiments, methods provided above
are implemented as a set of instructions contained on a
computer-accessible medium capable of directing a processor to
perform the respective method. In various embodiments, the medium
is a magnetic medium, an electronic medium, or an optical
medium.
[0090] Although specific embodiments have been illustrated and
described herein, it will be appreciated by those of ordinary skill
in the art that any arrangement which is calculated to achieve the
same purpose may be substituted for the specific embodiment shown.
This application is intended to cover adaptations or variations of
the present subject matter. It is to be understood that the above
description is intended to be illustrative, and not restrictive.
Combinations of the above embodiments as well as combinations of
portions of the above embodiments in other embodiments will be
apparent to those of skill in the art upon reviewing the above
description. The scope of the present subject matter should be
determined with reference to the appended claims, along with the
full scope of equivalents to which such claims are entitled.
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